Abstract

Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders.

Illustration of the tDCS device used to deliver the current stimulation. (a) The mouse is placed in a custom-made restraint box. The anode (contact area 3.5 mm2) is positioned over the left frontal cortex and the cathode (rubber-plate electrode, 9.5 cm2) onto the ventral thorax. A 2 × 20 min/day constant current of 0.2 mA is applied transcranially using a direct current stimulator (DC-Stimulator Plus) for five consecutive days, with a linear fade in/fade out of 10s. (b) The center of the electrode is positioned over the left frontal cortex 1 mm anterior to the coronal fissure and 1 mm left of the sagittal fissure (adapted from ). (c) Anode: a tubular plastic jacket (internal diameter: 2.1 mm) is surgically fixed onto the skull and filled with saline solution before the stimulation. The stimulation electrode is screwed into the tubular plastic jacket and dip in the saline solution. Only the saline solution is in contact with the skull.